onCARlytics (CF33-CD19)

P1, N=33, Recruiting, Imugene Limited | N=52 --> 33 | Trial completion date: Sep 2025 --> May 2029 | Trial primary completion date: Sep 2024 --> Jun 2027

P1, N=52, Recruiting, Imugene Limited | Not yet recruiting --> Recruiting

Currently, there are six systemic therapies available for patients with advanced disease including atezolizumab in combination with bevacizumab, lenvatinib, regorafenib, cabozantinib and ramucirumab while curative treatments include ablation, surgical resection, and liver transplantation...We have harnessed this capability of OV and developed a chimeric vaccinia-based OV called CF33-CD19t (onCARlytics) that delivers a non-signaling, truncated CD19 (CD19t) antigen to solid tumors allowing CD19-specific T cells to target them...In addition, this combination approach demonstrated impressive in vivo anti-tumor responses in a human xenograft HepG2 tumor model. By using this combination OV and CAR T cell strategy, we have now broadened the utility of CD19 ARTEMIS® T cells to otherwise target-less tumors such as HCC, which we anticipate can be applied to a wide array of solid cancers as an effective immunotherapy approach.

This combination approach demonstrated impressive in vivo anti-tumor response in human tumor xenograft models. Conclusions In summary, our results have demonstrated that further development of this combination immunotherapy for the potential treatment of a wide array of solid tumors is warranted.

Building on this, we generated an OV that expresses a non-signaling, truncated CD19 antigen (CF33-CD19t or onCARlytics, in collaboration with Imugene Limited), onto the surface of infected tumor cells prior to virus mediated tumor lysis, which redirected CD19-targeting chimeric antigen receptor (CAR) T cell activity against solid tumors (Park et al . Results Tumors infected with CF33-CD19t along with blinatumomab show specific tumor cell killing in vitro and robust anti-tumor efficacy using in vivo human triple-negative breast cancer xenograft models. Conclusions Using this approach, we show that a clinically-approved CD19-directed BiTE can be combined with oncolytic viruses to activate and redirect endogenous anti-tumor immunity against solid tumors.

For majority of patients with advanced-stage disease, treatment with agents such as sorafenib, lenvatinib, and atezolizumab/bevacizumab and other investigational agents yield modest success rates and justify the need for further development of new therapies. Results When administrated after onCARlytics, CD19 ARTEMIS® T cells were able to induce potent cytolytic activity against HCC tumor cells and demonstrated robust in vivo anti-tumor efficacy against human HCC tumor xenografts. Conclusions In summary, ARTEMIS® CD19 T cells combined with onCARlytics is a potentially effective immunotherapy strategy for the treatment of patients with HCC and can be applied to other solid tumors.